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Pediatr Res. 2014 Jan;75(1-2):165-70. doi: 10.1038/pr.2013.186. Epub 2013 Oct 28.

17q21 locus and ORMDL3: an increased risk for childhood asthma.

Author information

1
Department of Pediatrics, Weill Cornell Medical College, New York, New York.
2
1] Department of Pathology and Cell Biology, Columbia University, New York, New York [2] Department of Pediatrics, Columbia University, New York, New York [3] Institute of Human Nutrition, Columbia University, New York, New York.
3
1] Department of Pediatrics, Weill Cornell Medical College, New York, New York [2] Department of Genetic Medicine, Weill Cornell Medical College, New York, New York.

Abstract

Genetic variations in the 17q21 locus are strongly associated with childhood nonallergic asthma. Expression of the 17q21 genes, orosomucoid like 3 (ORMDL3) and gasdermin B (GSMDB), is affected by these disease-associated variants. However, until recently, no functional connection of the protein products coded by these genes with asthma was known. Lately, it has been identified that ORMDL3 function has been related to various cellular processes that could be relevant for the pathogenesis of asthma. This includes dysregulation of the unfolded protein response (UPR) associated with airway remodeling and also an effect of ORMDL3-dysregulated sphingolipid synthesis on bronchial hyperreactivity. These findings are crucial for a better understanding of the mechanism of childhood asthma and may lead to asthma therapeutics that target pathways previously not thought to be related to this common pediatric respiratory disease. Furthermore, this may validate the unbiased genome-wide association study (GWAS) approach for complex diseases such as asthma, to better define pathomechanisms and drug targets.

PMID:
24165737
DOI:
10.1038/pr.2013.186
[Indexed for MEDLINE]

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